MVA E2 recombinant vaccine in the treatment of human papillomavirus infection in men presenting intraurethral flat condyloma: a phase I/II study.

BACKGROUND: Human papillomavirus (HPV) is the etiologic agent for warts and cervical cancer. In Mexico, the death rate from cervical cancer is extremely high, and statistical data show that since 1990 the number of deaths is increasing. Condylomas and cancer of the penis are the most common lesions presented in men; bladder and prostate cancer in men are also associated with the presence of HPV. Since HPV is transmitted by sexual intercourse, treating both partners is necessary in order to eliminate the virus in the population. Approaches to this include preventative vaccines such as Gardasil, and therapeutic vaccines to treat established infections in both men and women. This will be the only way to decrease the numbers of deaths due to this malignancy. PATIENTS AND METHODS: We conducted a phase I/II clinical trial to evaluate the potential use of the recombinant vaccinia viral vaccine MVA E2 (composed of modified vaccinia virus Ankara [MVA] expressing the E2 gene of bovine papillomavirus) to treat flat condyloma lesions associated with oncogenic HPV in men. Fifty male patients with flat condyloma lesions were treated with either MVA E2 therapeutic vaccine or fluorouracil (5-fluorouracil). Thirty men received the therapeutic vaccine, at a total of 10(6) virus particles per dose, administered directly into the urethra once every week over a 4-week period. Twenty control patients were treated with 5% fluorouracil 1mL twice weekly over a 4-week period directly into the urethra. Reduction of lesions or absence of papillomavirus infection was monitored by colposcopy and histologic analysis. The immune response after MVA E2 treatment was determined by measuring the antibodies against the MVA E2 virus and by analyzing the lymphocyte cytotoxic activity against cancer cells bearing oncogenic papillomavirus. Presence of papillomavirus was determined by the Hybrid Capture method. RESULTS: Twenty-eight of 30 patients showed no lesion or presence of papillomavirus as diagnosed by colposcopy and brush histologic examination after 4 weeks of MVA E2 treatment. These patients showed complete elimination of flat condyloma in the urethra and no acetowhite spots were detected over the prepuce. In two other patients the acetowhite spots and flat condyloma did not diminish. All patients developed antibodies against the MVA E2 vaccine and E2 protein, and generated a specific cytotoxic response against papilloma-transformed cells. Viral DNA was not detected in MVA E2-treated patients. In the control group, 13 of 20 patients were free of lesions. Three of these patients had recurrence of lesions after 3 months of treatment and none of the patients developed specific antibodies against cancer cells. In contrast, patients treated with MVA E2 did not show any recurrence of lesions after 1 year of treatment. In addition, none of the patients had local or systemic adverse effects according to the WHO classification 1-4. CONCLUSIONS: Therapeutic vaccination with MVA E2 proved to be very effective in stimulating the immune system against papillomavirus, and in generating regression of flat condyloma lesions in men.

[Topical 5-fluorouracil for treatment of vaginal intraepithelial neoplasms]. / 5-fluorouracilo tópico en el tratamiento de la neoplasia intraepitelial vaginal.

OBJECTIVE: Our purpose was to determine the effectiveness of 5-fluorouracil (5-FU) in the treatment of vaginal intraepithelial neoplasia (VAIN). MATERIALS AND METHODS: The study was performed in 30 patients with a mean age of 54 years and previous diagnoses from reviewed records and histopathology slides selected from a group of 65 patients with VAIN from 1980 to 1998. Patients received intravaginal treatment with 5-FU, 1.5 g once weekly for 10 weeks and all patients were followed up for at least 2-years. Papanicolaou smear and colposcopy were performed, as was biopsy when indicated. RESULTS: Twenty eight (93%) patients with VAIN had prior or concurrent anogenital squamous neoplasia, including 5 with invasive cervical carcinoma and 23 with cervical intraepithelial neoplasia. In 23 of 30 treated patients (77%), VAIN went into remission after a single treatment; in 3, (10%), it went into remission after two treatment; 3 (10%) had recurrent VAIN 3; and in 1 (3%) it progressed to invasive vaginal cancer. The treatment was well tolerated. CONCLUSIONS: The 5-FU is an option choice for VAIN treatment. It is effective, with minimal slide effects. Its use should be confined to treating extensive or multifocal high-grade VAIN.

Edema masivo de ovario bilateral. Patología ginecológica poco frecuente. Informe de dos casos / Bilateral massive ovarian edema a not very frecuent gynecological disease. Two cases report

Se presentan dos casos de edema masivo bilateral de ovario, ocurridos en un hospital de concentración en los últimos cinco años. Se trata de una patología poco frecuente que afecta a mujeres jóvenes y fue descrita inicialmente por Kalstone en 1969. Este problema, puede ser uni o bilateral, este último, es poco frecuente y hasta el momento de la revisión se habían descrito diez casos en la literatura mundial. Los síntomas principales son: dolor y distensión abdominal, alteraciones menstruales, tumoración anexial y esterilidad. Una característica de esta patología es el rápido crecimiento del tamaño y volumen de los ovarios en corto tiempo. Desde el punto de vista histopatológico del dato principal es la presencia de edema intenso del estroma ovárico particularmente en la médula, sin detectarse elementos neoplásicos.El tratamiento habitual es la ooforectomía, aunque en casos bilaterales se ha sugerido la resección en cuña de ovarios con fijación de los mismos al útero para prevenir torciones ulteriores.Se concluye, que el edema masivo de ovario es una patología poco frecuente, que debe tenerse presente como causa de tumoración anexial y dolor abdominal en mujeres jóvenes con crecimiento rápido de la masa, en la cual no se identifican alteraciones neoplásicas.